Concurrent validity of supraclavicular skin temperature measured with iButtons and infrared thermography as a surrogate marker of brown adipose tissue

Brown adipose tissue (BAT) thermogenic activity is commonly assessed with a positron emission tomography with computed tomography scan (PET/CT). This technique has several limitations and alternative techniques are needed. Supraclavicular skin temperature measured with iButtons and infrared thermography (IRT) has been proposed as an indirect marker of BAT activity. We studied the concurrent validity of skin temperature measured with iButtons vs. IRT and the association of supraclavicular skin temperature measured with iButtons and IRT with BAT. We measured skin temperature upon a shivering threshold test with iButtons and IRT in 6 different regions in 12 participants (n = 2 men). On a separate day, we determined supraclavicular skin temperature with an iButton and IRT after 2 h of a personalized cooling protocol. Thereafter, we quantified BAT volume and activity by PET/CT. We observed that the absolute differences between the devices were statistically different from 0 (all P < 0.05) after the shivering threshold test. Moreover, we did not find any association between supraclavicular skin temperature measured with iButtons or IRT and BAT 18F-FDG activity (r = −0.213; P = 0.530 and r = −0.079; P = 0.817). However, we observed a negative association of supraclavicular skin temperature measured by IRT with BAT 18F-FDG volume (r = −0.764; P = 0.006), but not with supraclavicular skin temperature measured with iButtons (r = −0.546; P = 0.082). In light of these results, we concluded that the measurement of skin temperature obtained by iButtons and IRT are not comparable. Furthermore, it seems that supraclavicular skin temperature is not associated with BAT 18F-FDG activity, but it appears to be negatively associated with BAT 18F-FDG volume in the case of IRT

The Mediating Role of Brown Fat and Skeletal Muscle Measured by 18F-Fluorodeoxyglucose in the Thermoregulatory System in Young Adults

The authors would like to thank all the participants who took part in this investigation. This study is part of a PhD thesis conducted in the Biomedicine Doctoral Studies of the University of Granada, Spain. We are grateful to Alberto Quesada-Aranda for helping with the development of the Temperatus software (free trial at http://profith.ugr.es/ temperatus?lang=en). We are grateful to Ms Carmen Sainz-Quinn for assistance with English-language editingObjective: This study aimed to examine whether brown adipose tissue (BAT) or skeletal muscle activity mediates the relationship between personal level of environmental temperature (Personal-ET) and wrist skin temperature (WT). Moreover, we examined whether BAT and skeletal muscle have a mediating role between Personal-ET and WT (as a proxy of peripheral vasoconstriction/vasodilation). Methods: The levels of BAT were quantified by cold-induced 18F-fluorodeoxyglucose–positron emission tomography/computed tomography scan and measured the Personal-ET and WT by using iButtons (Maxim Integrated, Dallas, Texas) in 75 participants (74.6% women). Results: The study found that BAT volume and metabolic activity played a positive and significant role (up to 25.4%) in the association between Personal-ET and WT. In addition, at the coldest temperatures, the participants with lower levels of WT (inducing higher peripheral vasoconstriction) had higher levels of BAT outcomes, whereas in warm temperatures, participants with higher levels of WT (inducing higher peripheral vasodilation) had lower levels of BAT outcomes. The study did not find any mediating role of skeletal muscle activity. Conclusions: BAT volume and metabolic activity play a role in the relationship between Personal-ET and WT. Moreover, the data suggest that there are two distinct phenotypes: individuals who respond better to the cold, both through nonshivering thermogenesis and peripheral vasoconstriction, and individuals who respond better to the heat.This study was supported by the Spanish Ministry of Economy and Competitiveness, Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016‐79512‐R), and Fondos Estructurales de la Unión Europea (FEDER); by the Spanish Ministry of Education (FPU 13/04365); by the Fundación Iberoamericana de Nutrición; by the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022); by AstraZeneca HealthCare Foundation; by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES); and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR, Programa Contratos‐Puente. MAR is supported by a predoctoral research grant from University Jaume I (PREDOC/2015/13). AMN was supported by the Ministry of Economy and Competitiveness, the Instituto de Salud Carlos III through the Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CB16/10/00239), and grant 19899/GERM/15 (cofinanced by FEDER)

Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults

Funding for open access charge: Universidad de Granada/CBUA. This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393), by the Retos de la Sociedad program (DEP2016-79512-R), European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas de Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)-and Plan Propio de Investigacion 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctores, the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF; ref. SOMM17/6107/UGR), and the Fundacion Alfonso Martin Escudero (grant awarded to GSD).Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129.Universidad de Granada/CBUASpanish Government PI13/01393Retos de la Sociedad program DEP2016-79512-REuropean CommissionSpanish Government FPU13/04365Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018-the Programa Contratos-PuenteContratos Perfeccionamiento de DoctoresJunta de AndaluciaConsejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRFundacion Alfonso Martin Escuder

Diurnal variations of cold-induced thermogenesis in young, healthy adults: A randomized crossover trial

Background: Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating obesity and its related comorbidities. However, it has remained unclear whether CIT and BAT activity show diurnal variation in humans - knowledge that might allow treatments based on these factors to be time-optimized.Methods: A randomized crossover experiment was designed to examine whether CIT shows morning/evening variation in young, healthy adults (n = 14, 5 women). On the first experimental day, subjects' shivering thresholds were determined following a cooling protocol. After ≈96 h had elapsed, the subjects then returned on two further days (approx. 48 h apart) at 08:00 h or 18:00 in random order. On both the latter days, the resting energy expenditure (REE) was measured before the subjects underwent personalized cold exposure (i.e., according to their shivering threshold). CIT was then assessed for 60 min by indirect calorimetry. In an independent cross-sectional study (n = 133, 88 women), subjects came to the laboratory between 8:00 and 18:00 h and their BAT 18F-fluordeoxyglucose (18F-FDG) uptake was assessed after personalized cold stimulation.Results: Both the REE and CIT were similar in the morning and evening (all P > 0.05). Indeed, 60 min of personalized-mild cold exposure in the morning or evening elicited a similar change in energy expenditure (16.8 ± 12.8 vs. 15.7 ± 15.1% increase above REE, P = 0.72). BAT 18F-FDG uptake was also similar in the morning, evening and afternoon (all P > 0.05).Conclusion: CIT does not appear to show morning/evening variation in young healthy adults, with the current study design and methodology. BAT 18F-FDG uptake appears not to change across the day either, although experiments with a within-subject study design are needed to confirm these findings. Registered under ClinicalTrials.gov Identifier no. NCT02365129.</p

Cold exposure modulates potential brown adipokines in humans, but only FGF21 is associated with brown adipose tissue volume

Objective: The study objective was to investigate the effect of cold exposure on the plasma levels of five potential human brown adipokines (chemokine ligand 14 [CXCL14], growth differentiation factor 15 [GDF15], fibroblast growth factor 21 [FGF21], interleukin 6 [IL6], and bone morphogenic protein 8b [BMP8b]) and to study whether such cold-induced effects are related to brown adipose tissue (BAT) volume, activity, or radiodensity in young humans.Methods: Plasma levels of brown adipokines were measured before and 1 h and 2 h after starting an individualized cold exposure in 30 young adults (60% women, 21.9 +/- 2.3 y; 24.9 +/- 5.1 kg/m(2)). BAT volume, F-18-fluorodeoxyglucose uptake, and radiodensity were assessed by a static positron emission tomography-computerized tomography scan after cold exposure.Results: Cold exposure increased the concentration of CXCL14 (Delta 2h = 0.58 +/- 0.98 ng/mL; p = 0.007), GDF15 (Delta 2h = 19.63 +/- 46.2 pg/mL; p = 0.013), FGF21 (Delta 2h = 33.72 +/- 55.13 pg/mL; p = 0.003), and IL6 (Delta 1h = 1.98 +/- 3.56 pg/mL; p = 0.048) and reduced BMP8b (Delta 2h = -37.12 +/- 83.53 pg/mL; p = 0.022). The cold-induced increase in plasma FGF21 was positively associated with BAT volume (Delta 2h: beta = 0.456; R-2 = 0.307; p = 0.001), but not with F-18-fluorodeoxyglucose uptake or radiodensity. None of the changes in the other studied brown adipokines was related to BAT volume, activity, or radiodensity.Conclusions: Cold exposure modulates plasma levels of several potential brown adipokines in humans, whereas only cold-induced changes in FGF21 levels are associated with BAT volume. These findings suggest that human BAT might contribute to the circulatory pool of FGF21.Metabolic health: pathophysiological trajectories and therap

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial

Exercise modulates both brown adipose tissue (BAT)metabolismand white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n=31, and VIG-EX; n=31).We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6ml; Δ MOD-EX: −15.5 ± 62.1ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Spanish Government PI13/01393Retos de la Sociedad DEP2016-79512-R PTA-12264IEuropean CommissionSpanish Government FPU13/04365 FPU14/04172 FPU15/04059 FPU16/03653 FPU19/01609Consejo Nacional de Ciencia y Tecnologia (CONACyT) 440575Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018 -Programa Contratos-PuentePrograma Perfecionamiento de DoctoresJunta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRJunta de Andalucia P18-RT-4455Fundacion Alfonso Martin EscuderoMaria Zambrano fellowship by the Ministerio de Universidades y la Union Europea-NextGenerationEU RR_C_2021_04Novo Nordisk FoundationNovocure Limited NNF18OC003239

A larger brown fat volume and lower radiodensity are related to a greater cardiometabolic risk, especially in young men

Objectives: Brown adipose tissue (BAT) is important in the maintenance of cardiometabolic health in rodents. Recent reports appear to suggest the same in humans, although if this is true remains elusive partly because of the methodological bias that affected previous research. This cross-sectional work reports the relationships of cold-induced BAT volume, activity (peak standardized uptake, SUVpeak), and mean radiodensity (an inverse proxy of the triacylglycerols content) with the cardiometabolic and inflammatory profile of 131 young adults, and how these relationships are influenced by sex and body weight.Design: This is a cross-sectional study.Methods: Subjects underwent personalized cold exposure for 2 h to activate BAT, followed by static F-18-fluorodeoxyglucose PET-CT scanning to determine BAT variables. Information on cardiometabolic risk (CMR) and inflammatory markers was gathered, and a CMR score and fatty liver index (FLI) were calculated.Results: In men, BAT volume was positively related to homocysteine and liver damage markers concentrations (independently of BMI and seasonality) and the FLI (all P 0.05).Conclusions: A larger BAT volume and a lower BAT mean radiodensity are related to a higher CMR, especially in young men, which may support that BAT acts as a compensatory organ in states of metabolic disruption.</p

Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults

Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 +/- 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P <= 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129

Fecal microbiota composition is related to brown adipose tissue F-18-fluorodeoxyglucose uptake in young adults

Objective Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults. Methods 82 young adults (58 women, 21.8 +/- 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. F-18-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles. Results The relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho = 0.262, P = 0.213, P Conclusion Our results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings.</p